Trial Outcomes & Findings for A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression (NCT NCT02493868)
NCT ID: NCT02493868
Last Updated: 2025-04-29
Results Overview
Relapse is defined as any of following: Montgomery-asberg depression rating scale (MADRS) total score greater than or equal to (\>=) 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable remission: MADRS total score less than or equal to (\<=) 12 for at least 3 of last 4 weeks of OP phase, with 1 excursion total score greater than (\>) 12 or one missing assessment at OP week 13 or 14.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
719 participants
Primary outcome timeframe
Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)
Results posted on
2025-04-29
Participant Flow
Total of 719 participants were enrolled out of which 705 were included in the analysis. 14 participants were excluded due to premature closure of a site due to quality and data integrity issues.
Out of 705 participants, 437 (direct entry \[DE\] participants) entered in induction (IND) phase and 268 participants (150 transferred-entry \[TE\] participants from study ESKETINTRD3001 \[NCT02417064\] and 118 participants from study ESKETINTRD3002 \[NCT02418585\]) entered in this study in optimization (OP) phase.
Participant milestones
| Measure |
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD + Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance (MA) phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Induction Phase: DE Participants
STARTED
|
437
|
0
|
|
Induction Phase: DE Participants
COMPLETED
|
273
|
0
|
|
Induction Phase: DE Participants
NOT COMPLETED
|
164
|
0
|
|
Optimization Phase: DE+TE Participants
STARTED
|
455
|
86
|
|
Optimization Phase: DE+TE Participants
COMPLETED
|
297
|
54
|
|
Optimization Phase: DE+TE Participants
NOT COMPLETED
|
158
|
32
|
|
Maintenance Phase: DE+TE Participants
STARTED
|
152
|
199
|
|
Maintenance Phase: DE+TE Participants
Stable Remitters
|
90
|
86
|
|
Maintenance Phase: DE+TE Participants
Stable Responders
|
62
|
59
|
|
Maintenance Phase: DE+TE Participants
COMPLETED
|
139
|
177
|
|
Maintenance Phase: DE+TE Participants
NOT COMPLETED
|
13
|
22
|
|
Follow-up Phase
STARTED
|
481
|
64
|
|
Follow-up Phase
COMPLETED
|
470
|
62
|
|
Follow-up Phase
NOT COMPLETED
|
11
|
2
|
Reasons for withdrawal
| Measure |
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD + Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance (MA) phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Induction Phase: DE Participants
Adverse Event
|
22
|
0
|
|
Induction Phase: DE Participants
Lost to Follow-up
|
1
|
0
|
|
Induction Phase: DE Participants
Lack of Efficacy
|
2
|
0
|
|
Induction Phase: DE Participants
Protocol Violation
|
2
|
0
|
|
Induction Phase: DE Participants
Withdrawal by Subject
|
15
|
0
|
|
Induction Phase: DE Participants
Not meet criteria to continue next phase
|
114
|
0
|
|
Induction Phase: DE Participants
Other
|
8
|
0
|
|
Optimization Phase: DE+TE Participants
Adverse Event
|
5
|
0
|
|
Optimization Phase: DE+TE Participants
Lost to Follow-up
|
2
|
1
|
|
Optimization Phase: DE+TE Participants
Lack of Efficacy
|
8
|
0
|
|
Optimization Phase: DE+TE Participants
Protocol Violation
|
4
|
1
|
|
Optimization Phase: DE+TE Participants
Withdrawal by Subject
|
8
|
3
|
|
Optimization Phase: DE+TE Participants
MADRS >= 22 for 2 Consecutive Visit
|
14
|
5
|
|
Optimization Phase: DE+TE Participants
Not meet criteria to continue next phase
|
107
|
20
|
|
Optimization Phase: DE+TE Participants
Other
|
10
|
2
|
|
Maintenance Phase: DE+TE Participants
Adverse Event
|
1
|
4
|
|
Maintenance Phase: DE+TE Participants
Lost to Follow-up
|
1
|
0
|
|
Maintenance Phase: DE+TE Participants
Protocol Violation
|
1
|
1
|
|
Maintenance Phase: DE+TE Participants
Withdrawal by Subject
|
5
|
7
|
|
Maintenance Phase: DE+TE Participants
Pregnancy
|
1
|
0
|
|
Maintenance Phase: DE+TE Participants
Non Compliance with Study Drug
|
0
|
1
|
|
Maintenance Phase: DE+TE Participants
Other
|
4
|
9
|
|
Follow-up Phase
Lost to Follow-up
|
1
|
0
|
|
Follow-up Phase
Withdrawal by Subject
|
3
|
0
|
|
Follow-up Phase
Investigator Decision
|
5
|
1
|
|
Follow-up Phase
Other
|
2
|
1
|
Baseline Characteristics
A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression
Baseline characteristics by cohort
| Measure |
All Participants
n=705 Participants
All Participants (direct entry and transferred entry) who were enrolled in this study and received intranasal esketamine, matching placebo and oral antidepressant as per the assigned treatment.
|
|---|---|
|
Age, Continuous
|
46.1 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
457 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
248 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
94 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
600 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
31 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
71 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
38 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White Non-Hispanic
|
562 Participants
n=5 Participants
|
|
Region of Enrollment
BELGIUM
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
BRAZIL
|
64 Participants
n=5 Participants
|
|
Region of Enrollment
CANADA
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
CZECH REPUBLIC
|
99 Participants
n=5 Participants
|
|
Region of Enrollment
ESTONIA
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
FRANCE
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
GERMANY
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
HUNGARY
|
35 Participants
n=5 Participants
|
|
Region of Enrollment
ITALY
|
21 Participants
n=5 Participants
|
|
Region of Enrollment
MEXICO
|
35 Participants
n=5 Participants
|
|
Region of Enrollment
POLAND
|
132 Participants
n=5 Participants
|
|
Region of Enrollment
SLOVAKIA
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
SPAIN
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
SWEDEN
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
TURKEY
|
53 Participants
n=5 Participants
|
|
Region of Enrollment
UNITED STATES
|
190 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)Population: Full (stable remitters) analysis set included all the randomized participants who were in stable remission at the end of the optimization phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during the maintenance phase.
Relapse is defined as any of following: Montgomery-asberg depression rating scale (MADRS) total score greater than or equal to (\>=) 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable remission: MADRS total score less than or equal to (\<=) 12 for at least 3 of last 4 weeks of OP phase, with 1 excursion total score greater than (\>) 12 or one missing assessment at OP week 13 or 14.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=90 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=86 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Time to Relapse in Participants With Stable Remission (Maintenance Phase)
|
NA Days
Here NA signifies that median and 95%CI was not estimable due to not having sufficient events to meet the threshold for 50% on the Kaplan-Meier curve.
|
273.0 Days
Interval 97.0 to
Here NA signifies that upper limit of CI could not be estimated due to insufficient data.
|
SECONDARY outcome
Timeframe: Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)Population: Full (stable responders) analysis set included all randomized participants who were stable responders (who were not stable remitters) at the end of the optimization phase and who received at least 1 dose of intranasal study drug and 1 dose of oral antidepressant during the maintenance phase.
Relapse is defined as any of following: MADRS total score \>= 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable response is defined as \>= 50 percent (%) reduction in MADRS total score from baseline (Day 1 of induction phase, prior to first intranasal dose) in each of the last 2 weeks of the OP phase, but without meeting criteria for stable remission.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=62 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=59 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Time to Relapse in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
635.0 Days
Interval 264.0 to 635.0
|
88.0 Days
Interval 46.0 to 196.0
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable remitters) analysis set included all randomized participants who were in stable remission at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure (OM).
MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal - severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. The change from baseline in MADRS total score (last observation carried forward \[LOCF\] data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=89 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=86 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
|
7.5 Units on a scale
Standard Deviation 11.59
|
12.5 Units on a scale
Standard Deviation 13.63
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable responders) analysis set included all randomized participants who were stable responders (who were not stable remitters) at the end of the optimization phase and who received at least 1 dose of intranasal study drug and 1 dose of oral antidepressant during the maintenance phase.
MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal - severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. The change from baseline in MADRS total score (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=62 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=59 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
4.4 Units on a scale
Standard Deviation 11.38
|
11.4 Units on a scale
Standard Deviation 12.00
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
PHQ-9 is a 9-item, self-report scale assessing depressive symptoms. Each item is rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). The change from baseline in PHQ-9 total score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=89 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=86 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
|
3.3 Units on a scale
Standard Deviation 5.58
|
5.9 Units on a scale
Standard Deviation 7.09
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
PHQ-9 is a 9-item, self-report scale assessing depressive symptoms. Each item is rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). The change from baseline in PHQ-9 total score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=61 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=58 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in PHQ-9 Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
1.7 Units on a scale
Standard Deviation 5.02
|
4.7 Units on a scale
Standard Deviation 5.48
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The change from baseline in CGI-S score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=89 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=86 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
|
0.0 Units on a scale
Interval -3.0 to 4.0
|
1.0 Units on a scale
Interval -2.0 to 5.0
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. The change from baseline in CGI-S score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=62 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=58 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in Clinical Global Impression-Severity Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
0.0 Units on a scale
Interval -2.0 to 4.0
|
1.0 Units on a scale
Interval -3.0 to 5.0
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
GAD-7 is a brief and validated 7-item self-report assessment of overall anxiety. Participants respond to each item using a 4-point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15 -21). Item responses are summed to yield a total score (range of 0 to 21), with higher scores indicating more anxiety. The change from baseline in GAD-7 total score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=89 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=86 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in Generalized Anxiety Disorder-7 Items (GAD-7) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
|
2.2 Units on a scale
Standard Deviation 4.45
|
4.0 Units on a scale
Standard Deviation 5.93
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
GAD-7 is a brief and validated 7-item self-report assessment of overall anxiety. Participants respond to each item using a 4-point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15 -21). Item responses are summed to yield a total score (range of 0 to 21), with higher scores indicating more anxiety. The change from baseline in GAD-7 total score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=61 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=58 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in Generalized Anxiety Disorder-7 Items Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
1.4 Units on a scale
Standard Deviation 3.76
|
2.6 Units on a scale
Standard Deviation 4.26
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of optimization phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ VAS). EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a Health Status Index (HSI). HSI ranges from 0 (dead) to 1.00 (full health). EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) \*5. Higher score indicates worst health state.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=88 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=86 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Sum Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
|
7.5 Units on a scale
Standard Deviation 11.87
|
10.9 Units on a scale
Standard Deviation 14.74
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. The EQ VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine).
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=88 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=86 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in EQ Visual Analogue Scale Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
|
-10.4 Units on a scale
Standard Deviation 20.29
|
-16.1 Units on a scale
Standard Deviation 21.80
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a HSI. HSI ranges from 0 (dead) to 1.00 (full health).
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=88 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=86 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in EQ-5D-5L Health Status Index at Endpoint in Participants With Stable Remission (Maintenance Phase)
|
-0.067 Units on a scale
Standard Deviation 0.1180
|
-0.096 Units on a scale
Standard Deviation 0.1484
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a HSI. HSI ranges from 0 (dead) to 1.00 (full health). EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) \*5. Higher score indicates worst health state.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=61 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=58 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in EuroQol-5 Dimension-5 Level Sum Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
3.0 Units on a scale
Standard Deviation 8.13
|
8.4 Units on a scale
Standard Deviation 13.55
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. The EQ VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine).
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=61 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=59 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in EQ-5D-5L EQ Visual Analogue Scale Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
-1.3 Units on a scale
Standard Deviation 15.55
|
-13.8 Units on a scale
Standard Deviation 19.81
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a HSI. HSI ranges from 0 (dead) to 1.00 (full health).
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=61 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=58 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in EQ-5D-5L Health Status Index at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
-0.023 Units on a scale
Standard Deviation 0.0753
|
-0.073 Units on a scale
Standard Deviation 0.1383
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
The SDS is a participant-reported outcome measure and is a 5-item questionnaire used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1: work/school 2: social life 3: family life/home responsibilities using a 0-10 rating scale. It also has one item on days lost from school or work and one item on days when underproductive. The score for the first 3 items are summed to create a total score of 0-30 where a higher score indicates greater impairment. The recall period is 7 days. Scores \<= 4 for each item and \<= 12 for the total score are considered response. Scores \<= 2 for each item and \<= 6 for the total score are considered remission. The change from baseline in SDS total Score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=82 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=77 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
|
4.7 Units on a scale
Standard Deviation 7.34
|
7.2 Units on a scale
Standard Deviation 10.44
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (Up to 92 Weeks)Population: Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
The SDS is a participant-reported outcome measure and is a 5-item questionnaire used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1: work/school 2: social life 3: family life/home responsibilities using a 0-10 rating scale. It also has one item on days lost from school or work and one item on days when underproductive. The score for the first 3 items are summed to create a total score of 0-30 where a higher score indicates greater impairment. The recall period is 7 days. Scores \<= 4 for each item and \<= 12 for the total score are considered response. Scores \<= 2 for each item and \<= 6 for the total score are considered remission. The change from baseline in SDS total Score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Outcome measures
| Measure |
Intranasal Esketamine + Oral AD
n=58 Participants
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
Oral AD+ Intranasal Placebo
n=53 Participants
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
|
|---|---|---|
|
Change From Baseline in Sheehan Disability Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
|
2.2 Units on a scale
Standard Deviation 6.63
|
6.8 Units on a scale
Standard Deviation 7.64
|
Adverse Events
IND: Intranasal Esketamine + Oral AD
Serious events: 13 serious events
Other events: 306 other events
Deaths: 0 deaths
OP: Intranasal Esketamine + Oral AD
Serious events: 11 serious events
Other events: 279 other events
Deaths: 0 deaths
MA: Intranasal Esketamine + Oral AD
Serious events: 4 serious events
Other events: 114 other events
Deaths: 0 deaths
MA: Oral AD + Intranasal Placebo
Serious events: 1 serious events
Other events: 45 other events
Deaths: 0 deaths
FU: Intranasal Esketamine + Oral AD
Serious events: 3 serious events
Other events: 14 other events
Deaths: 0 deaths
FU: Oral AD + Intranasal Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
OP_TEP: Oral AD + Intranasal Placebo
Serious events: 0 serious events
Other events: 40 other events
Deaths: 0 deaths
MA_TEP: Oral AD + Intranasal Placebo
Serious events: 1 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
IND: Intranasal Esketamine + Oral AD
n=437 participants at risk
Open-label induction (IND) phase (direct-entry participants only): received 56 milligram (mg) or 84 mg intranasal esketamine solution twice weekly with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks.
|
OP: Intranasal Esketamine + Oral AD
n=455 participants at risk
Optimization (OP) phase (both direct-entry and transferred-entry participants): received 56 mg or 84 mg intranasal esketamine solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks.
|
MA: Intranasal Esketamine + Oral AD
n=152 participants at risk
Maintenance (MA) phase (both direct-entry and transferred-entry participants): received 56 mg or 84 mg intranasal esketamine solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily until relapse or study termination.
|
MA: Oral AD + Intranasal Placebo
n=145 participants at risk
Maintenance phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), until relapse or study termination.
|
FU: Intranasal Esketamine + Oral AD
n=481 participants at risk
Participants (who were non-responders in IND phase and who were in OP and MA phase at study termination) who received at least 1 dose of 56 mg or 84 mg intranasal esketamine participated in the follow-up (FU) phase. No intranasal esketamine was administered during FU phase. Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate.
|
FU: Oral AD + Intranasal Placebo
n=64 participants at risk
Participants (who were non-responders in IND phase and who were in OP and MA phase at study termination) who received intranasal esketamine matching placebo with oral AD participated in the FU phase. Participants received oral AD for at least the 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate.
|
OP_TEP: Oral AD + Intranasal Placebo
n=86 participants at risk
OP phase (transferred-entry participants \[TEP\]): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks.
|
MA_TEP: Oral AD + Intranasal Placebo
n=54 participants at risk
Maintenance phase (transferred-entry participants): Participants were randomized (at the end of optimization phase) to intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR).
|
|---|---|---|---|---|---|---|---|---|
|
Renal and urinary disorders
Nephrolithiasis
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Vascular disorders
Hypertensive Crisis
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Cardiac disorders
Sinus Tachycardia
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Gastrointestinal disorders
Anal Fissure
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
General disorders
Chest Pain
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.21%
1/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
General disorders
Hypothermia
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Hepatobiliary disorders
Cholecystitis Acute
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Infections and infestations
Sepsis
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Injury, poisoning and procedural complications
Procedural Pain
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.21%
1/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Autonomic Nervous System Imbalance
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Headache
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Lacunar Stroke
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Migraine
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Sedation
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Simple Partial Seizures
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Pregnancy, puerperium and perinatal conditions
Ectopic Pregnancy
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.66%
1/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Anxiety
|
0.46%
2/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Depression
|
0.69%
3/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
1.3%
2/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.69%
1/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.21%
1/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Disorientation
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Major Depression
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.66%
1/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Mania
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.21%
1/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Panic Attack
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.22%
1/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Suicidal Ideation
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Vascular disorders
Orthostatic Hypotension
|
0.23%
1/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Injury, poisoning and procedural complications
Clavicle Fracture
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
1.9%
1/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
Other adverse events
| Measure |
IND: Intranasal Esketamine + Oral AD
n=437 participants at risk
Open-label induction (IND) phase (direct-entry participants only): received 56 milligram (mg) or 84 mg intranasal esketamine solution twice weekly with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]), once daily for 4 weeks.
|
OP: Intranasal Esketamine + Oral AD
n=455 participants at risk
Optimization (OP) phase (both direct-entry and transferred-entry participants): received 56 mg or 84 mg intranasal esketamine solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks.
|
MA: Intranasal Esketamine + Oral AD
n=152 participants at risk
Maintenance (MA) phase (both direct-entry and transferred-entry participants): received 56 mg or 84 mg intranasal esketamine solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily until relapse or study termination.
|
MA: Oral AD + Intranasal Placebo
n=145 participants at risk
Maintenance phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), until relapse or study termination.
|
FU: Intranasal Esketamine + Oral AD
n=481 participants at risk
Participants (who were non-responders in IND phase and who were in OP and MA phase at study termination) who received at least 1 dose of 56 mg or 84 mg intranasal esketamine participated in the follow-up (FU) phase. No intranasal esketamine was administered during FU phase. Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate.
|
FU: Oral AD + Intranasal Placebo
n=64 participants at risk
Participants (who were non-responders in IND phase and who were in OP and MA phase at study termination) who received intranasal esketamine matching placebo with oral AD participated in the FU phase. Participants received oral AD for at least the 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate.
|
OP_TEP: Oral AD + Intranasal Placebo
n=86 participants at risk
OP phase (transferred-entry participants \[TEP\]): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks.
|
MA_TEP: Oral AD + Intranasal Placebo
n=54 participants at risk
Maintenance phase (transferred-entry participants): Participants were randomized (at the end of optimization phase) to intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR).
|
|---|---|---|---|---|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
22.7%
99/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
20.0%
91/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
25.0%
38/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.5%
8/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.42%
2/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Eye disorders
Diplopia
|
3.7%
16/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
2.2%
10/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.9%
9/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Eye disorders
Vision Blurred
|
10.3%
45/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
6.6%
30/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
15.8%
24/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.69%
1/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Gastrointestinal disorders
Hypoaesthesia Oral
|
7.3%
32/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
7.5%
34/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
13.2%
20/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Gastrointestinal disorders
Nausea
|
21.5%
94/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
10.5%
48/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
16.4%
25/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.69%
1/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.42%
2/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
1.6%
1/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.6%
3/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Gastrointestinal disorders
Paraesthesia Oral
|
3.7%
16/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
2.9%
13/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.3%
8/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.69%
1/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Gastrointestinal disorders
Vomiting
|
6.6%
29/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
3.7%
17/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
6.6%
10/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.69%
1/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
1.1%
5/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
4.8%
22/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
7.2%
11/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
8.3%
12/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.21%
1/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
24.1%
13/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Investigations
Blood Pressure Increased
|
7.8%
34/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.7%
26/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
6.6%
10/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
3.4%
5/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Dizziness
|
22.2%
97/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
13.4%
61/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
20.4%
31/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
4.8%
7/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
1.6%
1/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
7.0%
6/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Dizziness Postural
|
7.6%
33/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.7%
26/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
6.6%
10/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
2.1%
3/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Dysgeusia
|
20.6%
90/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
17.4%
79/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
27.0%
41/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
6.9%
10/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
9.3%
8/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
14.8%
8/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Headache
|
13.7%
60/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
12.5%
57/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
17.8%
27/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
9.7%
14/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
1.7%
8/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
18.6%
16/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
22.2%
12/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Hypoaesthesia
|
6.9%
30/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.3%
24/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.9%
9/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Paraesthesia
|
11.0%
48/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.1%
23/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
7.2%
11/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Sedation
|
9.8%
43/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
4.2%
19/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
6.6%
10/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.69%
1/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Nervous system disorders
Somnolence
|
14.9%
65/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
13.8%
63/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
21.1%
32/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
2.1%
3/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.8%
5/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
7.4%
4/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Anxiety
|
7.1%
31/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
2.4%
11/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
7.9%
12/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
3.4%
5/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.42%
2/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.8%
5/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Confusional State
|
3.0%
13/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
2.0%
9/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.9%
9/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Psychiatric disorders
Dissociation
|
18.8%
82/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
16.0%
73/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
23.0%
35/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Discomfort
|
6.6%
29/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.7%
26/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
7.2%
11/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
2.8%
4/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Respiratory, thoracic and mediastinal disorders
Throat Irritation
|
5.9%
26/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
3.5%
16/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.3%
8/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.69%
1/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
7.4%
4/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.6%
3/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.6%
3/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
|
Musculoskeletal and connective tissue disorders
Spinal Pain
|
0.00%
0/437 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/455 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/152 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/145 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/481 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/64 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
0.00%
0/86 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
5.6%
3/54 • Up to 2 years
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
|
Additional Information
Senior Director, Clinical Research
Janssen Research & Development, LLC
Phone: 844-434-4210
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER